Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy
Autor: | Norberto Peporine Lopes, José Luiz Liberato, Wagner Ferreira dos Santos, Andréia Cristina Karklin Fontana, Márcia Renata Mortari, Lívea Dornela Godoy, Rene Oliveira Beleboni, Alexandra Olimpio Siqueira Cunha |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Parawixia bistriata Health Toxicology and Mutagenesis medicine.medical_treatment spider toxin Spider Venoms lcsh:Medicine Toxicology Hippocampus chemistry.chemical_compound Epilepsy 0302 clinical medicine pilocarpine model Urea Neurons temporal lobe epilepsy Riluzole Neuroprotective Agents Neuroprotective Agents/therapeutic use GABAergic neuroprotection medicine.symptom GABA uptake inhibitor medicine.drug Parawixin2 Status epilepticus Neuroprotection Article 03 medical and health sciences medicine Nipecotic acid Animals Hippocampus/drug effects Rats Wistar Hippocampal sclerosis business.industry lcsh:R medicine.disease Spider Venoms/therapeutic use Urea/analogs & derivatives Neurons/drug effects Epilepsy Temporal Lobe/drug therapy VENENOS DE ORIGEM ANIMAL Disease Models Animal 030104 developmental biology Anticonvulsant Epilepsy Temporal Lobe chemistry nervous system hippocampal lost cells business Neuroscience 030217 neurology & neurosurgery |
Zdroj: | Liberato, J L, Godoy, L D, Cunha, A O S, Mortari, M R, de Oliveira Beleboni, R, Fontana, A C K, Lopes, N P & Dos Santos, W F 2018, ' Parawixin2 Protects Hippocampal Cells in Experimental Temporal Lobe Epilepsy ', Toxins, vol. 10, no. 12 . https://doi.org/10.3390/toxins10120486 Toxins Volume 10 Issue 12 Toxins, Vol 10, Iss 12, p 486 (2018) Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
DOI: | 10.3390/toxins10120486 |
Popis: | Epilepsy is considered as one of the major disabling neuropathologies. Almost one third of adult patients with temporal lobe epilepsy (TLE) do not respond to current antiepileptic drugs (AEDs). Additionally, most AEDs do not have neuroprotective effects against the inherent neurodegenerative process underlying the hippocampal sclerosis on TLE. Dysfunctions in the GABAergic neurotransmission may contribute not only to the onset of epileptic activity but also constitute an important system for therapeutic approaches. Therefore, molecules that enhance GABA inhibitory effects could open novel avenues for the understanding of epileptic plasticity and for drug development. Parawixin2, a compound isolated from Parawixia bistriata spider venom, inhibits both GABA and glycine uptake and has an anticonvulsant effect against a wide range of chemoconvulsants. The neuroprotective potential of Parawixin2 was analyzed in a model of TLE induced by a long-lasting Status Epilepticus (SE), and its efficiency was compared to well-known neuroprotective drugs, such as riluzole and nipecotic acid. Neuroprotection was assessed through histological markers for cell density (Nissl), astrocytic reactivity (GFAP) and cell death labeling (TUNEL), which were performed 24 h and 72 h after SE. Parawixin2 treatment resulted in neuroprotective effects in a dose dependent manner at 24 h and 72 h after SE, as well as reduced reactive astrocytes and apoptotic cell death. Based on these findings, Parawixin2 has a great potential to be used as a tool for neuroscience research and as a probe to the development of novel GABAergic neuroprotective agents. |
Databáze: | OpenAIRE |
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